SCN5A Variant G274C

Summary of observed carriers, functional annotations, and structural context for SCN5A G274C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

18%

1/11 effective observations

Estimated BrS1 penetrance

19%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

G274C is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-8.78 1 0.56 0.977 22 16

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
Literature, cohort, and gnomAD 1 1 0 0
Variant features alone 15 12 1 2

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near G274C.
Neighbour residue Distance (Å) Observed variants
328 13
364 14
277 4
271 10 L271V,
266 14 L266H,
326 13
276 5 L276Q, L276P,
348 11 P348A,
270 10 Q270K,
360 13
279 10
385 10 A385T,
1552 13 Q1552R, Q1552L,
355 8 F355I, F355C,
1549 10
278 6 H278D, H278R,
356 7 D356N,
361 12
343 6
327 12
384 9 S384T,
354 7
329 14
386 13 G386R, G386R, G386E,
349 15 D349N,
267 14
1550 6
357 11
272 7
341 11 C341Y,
274 0 G274C,
273 5
325 11 L325R,
392 15
324 15
389 13 Y389H, Y389X,
269 9
1620 14 T1620K, T1620M,
345 10
275 4 N275K, N275K,
383 14
280 14 C280Y,
323 14
347 9
382 14
1548 12 E1548K, G1548K,
351 12 G351S, G351C, G351D, G351V,
265 14 A265V,
1619 15 P1619Q, P1619L, c.4856delC,
358 14
342 11
1551 9 D1551N, D1551Y,
346 11 E346K, E346G, E346X, E346D, E346D,
359 14 A359T, p.A359PfsX12,
344 9 A344S,
381 10 c.1140+1G>A, c.1141-3C>A,
352 14 Y352C,
380 12
268 10 G268S,
377 13
281 15 V281M,
353 10 T353I,
1623 14 c.4867delC, R1623X, R1623Q, R1623L